The South American Plains Vizcacha, Lagostomus maximus, as a Valuable Animal Model for Reproductive Studies
- 1. Centro de Estudios Biomédicos, Biotecnológicos, AmbienCentro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico, Universidad Maimónides, Argentinanóstico, Universidad Maimónides, Argentina
- 2. Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina
Citation
Dorfman VB, Felipe Inserra PI, Leopardo NP, Halperin J, Vitullo AD (2016) The South American Plains Vizcacha, Lagostomus maximus, as a Valuable Animal Model for Reproductive Studies. JSM Anat Physiol 1(1): 1004.
INTRODUCTION
The vast majority of our understanding of the mammalian reproductive biology comes from investigations mainly performed in mice, rats and humans. However, evidence gathered from non-conventional laboratory models, farm and wild animals strongly suggests that reproductive mechanisms show a plethora of different strategies among species. For instance, studies developed in unconventional rodents such as guinea pigs and hamsters, that share with humans some endocrine and reproductive characters, have contributed to a better understanding of human physiology and disease [1,2]. A better knowledge on the variety of mechanisms that regulate reproduction could lead to improve early diagnosis, treatment, or novel strategies development to ameliorate fertility and guarantee a successful reproduction. In this letter, we briefly introduce Lagostomus maximus, an unconventional rodent whose neuroendocrinology and reproduction in general have attracted significant interest in recent years in view of its unusual reproductive traits.
Reproductive physiology and endocrinology of the plains vizcacha
The South American plains vizcacha, L. maximus, a hystricognathi fossorial rodent that inhabits the Pampean region of Argentina [3], exhibits certain peculiar reproductive features that stand out from most mammalian species. In the 70`s, this rodent was found to be the major poly-ovulatory species among mammals, with the ability to release up to 800 oocytes per estral cycle [4]. Despite the extreme poly-ovulatory rate, 8 to 10 oocytes are successfully fertilized and implanted in the uterus, and only one or two embryos are gestated to term [5]. This high ovulatory rate is closely related to several physiological aspects of the ovary: i) a greatly convoluted anatomy of the ovary that increases the surface for ovulation, ii) the small size of the ovulatory follicles [5], and iii) a preferential expression of the anti-apoptotic BCL-2 over the pro-apoptotic BAX protein which leads to a down-regulation of apoptotic pathways and promotes a continuous oocyte production [6,7]. Moreover, the inversion in the BAX/BCL-2 balance is expressed in embryonic ovaries throughout development, pinpointing this physiological aspect as a constitutive feature of the vizcacha´s ovary, which precludes massive intra-ovarian germ cell elimination. Massive intraovarian germ cell elimination through apoptosis during fetal life accounts for 66 to 85% loss at birth as recorded for human, mouse and rat [8]. On the contrary, female germ line in the vizcacha develops in the absence of germ cell attrition during fetal life and germ cell population rises continuously from colonization of the genital ridges until birth [9].
Other noteworthy features of the vizcachas’ reproductive biology are the uninterrupted pre-ovulatory follicle formation throughout the 155-day lasting pregnancy and the pseudoovulatory process that takes place at mid-gestation and adds up numerous secondary corpora lutea with oocyte retention [10-11]. This latter event divides the vizcachas’ gestation into two well defined phases: before and after pseudo-ovulation. During the first phase, from implantation until around day 70 of gestation, circulating progesterone gradually decreases as a result of decay in corpora lutea activity [12]; however, embryos are still too immature to be born. Approximately at gestation day 90, when circulating progesterone reaches its minimum level, only the two embryos nearest the cervix survive whereas most proximal embryos suffered a progressive elimination through a natural resorption process. At this point, a new wave of follicular recruitment, pseudo-ovulation and follicular luteinization is triggered. Consequently, progesterone released from the newly developed corpora lutea progressively increases throughout the second half of gestation saving distal embryos from degeneration and allowing their development to term [10-12]. As a secondary effect, the increased levels of progesterone favor a precociousdevelopment of the mammary gland, preparing females to face the nutritional demand of fully developed newborns [13].
During gestation of most mammals, increased ovarian steroid levels induce a negative feedback over the hypothalamichypophyseal-ovary (HHO) axis keeping it inhibited till the end of pregnancy [14-16]. The pseudo-ovulatory event at mid-gestation exhibited by L. maximus is only possible with a reactivation of the HHO axis. We have already demonstrated HHO axis activity throughout the second half of gestation in spite of high hormone levels. Particularly, gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) significantly increase their expression around gestational day 100-120, together with ovarian progesterone and estradiol [10].
The distribution of GnRH in the hypothalamus of the vizcacha shows similarities with other mammals. In addition, GnRH neurons are also localized in the supraoptic nucleus (SON) [17]. This localization of GnRH neurons has been reported only in the domestic pig, another recognized poly-ovulatory mammal [18]. The co-localization of progesterone receptor or estrogen receptor alpha with GnRH in neurons of the medial preoptic area and SON suggests a direct regulation of GnRH expression by progesterone and estradiol in opposition to the indirect model of GnRH regulation by ovarian hormones classically described [10,19].
This particular strategy developed by vizcacha, allows a greater sensitivity of GnRH neurons to sense changes in steroid levels which eventually trigger ovulation during pregnancy. Female vizcachas also exhibit a significant increase in serum LH at mid-gestation, although oocyte extrusion is rarely observed. Instead, follicular luteinization with oocyte retention is mostly detected and the morphological evidence of such event is the ovulatory stigmata [10,11].
CONCLUSION
The peculiar reproductive features mentioned above situate vizcacha as a valuable animal model for the development of studies in reproductive biology. In this sense, vizcacha is positioned as a mammal with a unique strategy that warrants reproductive success. Such a different strategy, far from being an oddity, offers a useful possibility To explore other expression patterns in conserved gene networks and to identify molecular markers that can be evaluated as potential targets of therapeutic interest. This may help to develop novel treatments against female infertility conditions such as premature menopause, hypothalamic amenorrhea and oligomenorrhea, and vulnerability to diseases such as polycystic ovary syndrome, or complications during pregnancy.
ACKNOWLEDGEMENTS
This work was supported by CONICET (PIP Nº 110/14), PICT 2014-1281 and by Fundación Científica Felipe Fiorellino, Universidad Maimónides, Argentina. We are especially grateful to the Ministerio de Asuntos Agrarios, Dirección de Flora y Fauna, Buenos Aires Province for authorizing animal capture at the Estación de Cría de Animales Silvestres (ECAS) and to the personnel of ECAS for their invaluable help in trapping and handling of animals.
REFERENCES
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12.Fraunhoffer N. Renovación de masa germinal ovárica en un modelo animal poliovulatorio (Lagostomus maximus) y en la Endometriosis ovárica humana. PhD Thesis. Facultad de Medicina, Universidad de Buenos Aires. 2014.
19.Inserra, PIF, Charif SE, Rey-Funes M, Saucedo L, Di Giorgio NP, LuxLantos V, et al. Hypothalamic - Hypophyseal - Gonadal axis activity in the South American plains vizcacha during gestation. Histology and Histopathology, Cellular and Molecular Biology. 2014; 28: 87.
